Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
Naunyn Schmiedebergs Arch Pharmacol. 2010 Jan;381(1):73-81. doi: 10.1007/s00210-009-0470-4. Epub 2009 Nov 20.
L-glutamate plays a key role in neuronal cell death associated with many neurodegenerative conditions such as cerebral ischemia, hypoxia, Alzheimer's, Huntington's, and Parkinson's diseases. Selaginellin, a component extracted from Saussurea pulvinata (Hook.et Grev.) Maximo, was assessed for its ability to protect rat pheochromocytoma (PC12) cells against oxidative toxicity induced by glutamate. The differentiated PC12 cells were pretreated with various concentrations (10(-7), 3 x 10(-7), or 10(-6) M) of selaginellin for 1 h prior to exposure to L-glutamate. Selaginellin was shown to protect PC12 cells against glutamate toxicity, as determined by characteristic morphological features, lactate dehydrogenase release and cell viability, and apoptosis as evaluated by Hoechst 33342 staining assay and caspase-3 activity. In addition, the increase in levels of reactive oxygen species and decrease in klotho gene expression induced by glutamate were significantly reversed by selaginellin. Our study suggests that selaginellin has a neuroprotective effect against L-glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis via scavenging reactive oxygen species and up-regulating the expression of klotho gene.
L-谷氨酸在与许多神经退行性疾病相关的神经元细胞死亡中起关键作用，如脑缺血、缺氧、阿尔茨海默病、亨廷顿病和帕金森病。从天山雪莲中提取的卷柏素被评估为其保护大鼠嗜铬细胞瘤（PC12）细胞免受谷氨酸诱导的氧化毒性的能力。分化的 PC12 细胞在用 L-谷氨酸孵育之前用不同浓度（10（-7）、3 x 10（-7）或 10（-6）M）的卷柏素预处理 1 小时。通过特征性形态特征、乳酸脱氢酶释放和细胞活力以及通过 Hoechst 33342 染色测定法和 caspase-3 活性评估的细胞凋亡，表明卷柏素可保护 PC12 细胞免受谷氨酸毒性。此外，谷氨酸诱导的活性氧水平升高和 klotho 基因表达降低明显被卷柏素逆转。我们的研究表明，卷柏素通过清除活性氧和上调 klotho 基因的表达来发挥抗氧化和抗凋亡作用，从而具有对抗 L-谷氨酸诱导的神经毒性的神经保护作用。
